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The NCDR has a strong interest in defining cellular/molecular mechanisms underlying neurodegeneration, neuroinflammation and regeneration in the eye/visual system of teleost fish and rodents.
The quest for neuroprotective and/or regenerative therapies to tackle neurodegenerative disorders and central nervous system (CNS) trauma continues to be a central theme in our research.
(for more info see: http://bio.kuleuven.be/df/LM/).
Despite intensive research efforts, induction of regeneration and subsequent functional recovery of the injured mammalian CNS remains a challenge, which makes the search for new pro-regenerative molecules essential, especially in an aging environment. In contrast to mammals, teleost fish have a remarkable neurogenic and regenerative potential in their adult CNS, already making them a preferred model organism to study the contribution of intrinsic and extrinsic molecular players to successful regeneration. Moreover, over the past decade, several teleost species, such as the zebrafish (Danio rerio) and the African turquoise killifish (Nothobranchius furzeri), have been exploited in gerontology research. They are ideally suited for research into maintaining and/or restoring brain function upon aging and to identify aging mechanisms that might underlie a flawed regeneration in adult mammals.
Besides a special interest in defining the role of neuroinflammatory processes in axon regeneration, we study an essential component of the neuronal circuitry overlooked for decades: the dendrites. Based on intriguing findings in zebrafish, we hypothesize an antagonistic interplay between dendritic remodeling and axon regrowth in the damaged fish CNS and are pursuing energy channeling as an underlying mechanism, specifically focusing on mitochondrial dynamics and bioenergetics driving neurite regeneration. Within our aging neurobiology research, we exploit the visual system of the fast-aging killifish to study stem cell exhaustion, neurodegeneration and regeneration, axonal and synaptic integrity/regrowth, de- and remyelination, gliosis and microglial reactivity, and envision drug discovery and target validation activities in the field of healthy brain aging and age-related neurodegenerative diseases.
Notably, the retina/retinotectal system forms a robust model since physiological and disease processes occurring in the retina are indicators of similar processes occurring elsewhere in the CNS, and vice versa. To tackle our research questions, we follow a multidisciplinary approach in which advanced in vivo ocular imaging technologies and visual function tests are being combined with detailed morphological phenotyping, using confocal/multiphoton/light-sheet microscopy, optical clearing and time-lapse imaging, and longitudinal and post-mortem morphometrical analyses to follow inflammatory and de/regenerative processes. Besides, ex vivo/in vitro retinal tissue/cell cultures, state-of-the-art opto- & chemogenetic, cell sorting and (single-cell) omics approaches are available to further study the cellular and molecular pathways underlying neuroprotection/regeneration. All research runs within the ‘Vision Core Leuven’, a preclinical animal platform which brings together cutting-edge technologies within the field of ocular imaging, electrophysiology and visual function testing in laboratory animals (see: http://www.visioncore.be/).
Within the aforementioned research lines, we are looking for a motivated post-doc willing to supervise the fish-related research.
Financing is available, but an application for a Marie Skłodowska-Curie Actions Individual Fellowship, Belgian FWO post-doctoral fellowship or equivalent is preferred.